The device is a box containing lyophilized pooled plasmas from donors genotyped for the factor V Leiden mutation (FV : Q506) to be reconstituted with water by the user. Controls on the factor plasmas of either donors with helerazurous EV: O56 minuter by the user. Con plasmas of either donors with heterozygous FV:Q506 mutation or normal wild-type pattern. These controls are intended to be your for wolf These controls are intended to be used for quality assurance in connection with the IVD device 'Pefakit® APC-R Factor V Leiden'.

Device Description

Pefakit® APC-R Factor V Leiden Controls is an in vitro diagnostic controls kit containing 3 vials each of the following 2 Ivophilized plasmas: C1: pooled human plasma from donors confirmed to be normal wild-type by FV Leiden PCR testing C2: pooled human plasma from donors confirmed to be heterozygous by FV Leiden PCR testing.

AI/ML Overview

The provided 510(k) summary for "Pefakit® APC-R Factor V Leiden Controls" does not contain detailed acceptance criteria or a specific study designed to prove that the device meets those criteria in the way a diagnostic imaging or AI-based device submission might. This device is a quality control product, and its evaluation focuses on demonstrating substantial equivalence to a predicate device and stability, rather than diagnostic performance against specific metrics like sensitivity or specificity.

However, based on the information provided, we can infer some "acceptance criteria" related to its function as a control and summarize the relevant studies.

Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Inferred)	Reported Device Performance
Stability (Reconstituted, On-board)	At least 8 hours
Stability (Reconstituted, Frozen at -20°C)	At least 6 months
Stability (Unopened kit at 2-8°C)	Proved stable for 2 years (real-time long-term studies ongoing)
Batch-to-Batch Variability	Very low (demonstrated on three pilot batches of increasing size: 100, 250, and 1000 device boxes)
Suitability for Intended Use (Quality Control & Validation)	Proved suitable for its intended use and equivalent to the control plasmas in the predicate device (COATEST® APC™ RESISTANCE V) in clinical studies conducted at two major hospitals. This implies the controls provided appropriate results (e.g., clotting times and ratio values within expected ranges for the respective genotypes) for quality assurance.
Safety (Absence of viruses)	Screened for absence of viruses (HIV1&2, HCV, HBV, and HTLV I&II) by FDA-approved methods.
Genotype Confirmation	Human plasma from donors confirmed to be normal wild-type or heterozygous by FV Leiden PCR testing.

Study Details

The primary "study" supporting this device is comprised of non-clinical tests for stability and batch variability, and clinical studies where these controls were used in conjunction with the principal diagnostic device (Pefakit® APC-R Factor V Leiden) to demonstrate its own substantial equivalence, implicitly validating the controls.

1. Sample size used for the test set and the data provenance:

Non-clinical (Batch-to-batch variability): Three pilot batches of increasing size (100, 250, and 1000 device boxes) were used. Data provenance is "in-house."
Clinical (Suitability for intended use): The controls were used in "clinical studies" for the basic test device (Pefakit® APC-R Factor V Leiden). These studies were conducted at "two haematology laboratories of big central Hospitals in Europe (Clinical Institute for Medical and Chemical Laboratory Diagnostics/Allgemeines Krankenhaus [CIMCLD/AKH], Vienna) and the USA (Duke University Medical Center [DUMC], Durham/Raleigh NC)." The report does not specify the number of patient samples (cases) or control runs used during these clinical studies, nor if it was retrospective or prospective, though it implies prospective use within larger test validation.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

For the controls themselves: The genotyping of pooled human plasma donors for Factor V Leiden (normal wild-type and heterozygous) was confirmed by "FV Leiden PCR testing." The individuals or experts performing this PCR testing and interpreting the results are not specified, nor are their qualifications. This is the "ground truth" for the control material itself.
For the clinical studies: The "clinical studies" were performed at "two haematology laboratories." The experts involved in generating the results and assessing the suitability of the controls would be laboratory personnel and medical professionals at these sites, but their specific number and qualifications are not detailed.

3. Adjudication method for the test set:

For the non-clinical stability and batch variability tests, no adjudication method is mentioned, as these are objective measurements.
For the clinical studies where the controls were used, no specific adjudication method is described for the evaluation of the controls. The controls were stated to "prove suitable" and "equivalent," implying a successful outcome based on laboratory protocols.

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

Not applicable. This device is a quality control reagent, not an AI-assisted diagnostic tool. No MRMC study was conducted.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

Partially applicable/Inferred. The non-clinical stability and batch variability tests could be considered "standalone" as they evaluate the product's intrinsic properties. The "testing" itself (e.g., clotting time measurements) would be performed by lab equipment (an "algorithm" in a broad sense, or an automated process) and then interpreted by human operators. However, this is not an AI algorithm.

6. The type of ground truth used:

Molecular (PCR testing): The "ground truth" for the control material (C1 and C2) is the confirmed genotype of the pooled human plasma donors, established by FV Leiden PCR testing.

7. The sample size for the training set:

Not applicable. This is a quality control product, not a machine learning algorithm that requires a training set. The "samples" referred to are the batches of control material and the donors from whom the plasma was collected.

8. How the ground truth for the training set was established:

Not applicable. (See point 7). However, the ground truth for the source plasma was established via "FV Leiden PCR testing."

Summary

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6042760

DEC 22 2004

510(k) SUMMARY

Pefakit® APC-R Factor V Leiden Controls

In accordance with the requirements of Safe Medical Devices Act (SMDA) of 1990, a 510(k) summary is provided as outlined in 21 CFR 807.92.

Part A

1. Submitter's name, address, telephone number, contact person, and the date the summary was prepared

Submitter's Name:	Pentapharm Ltd.
Submitter's Address:	Engelgasse 109
	CH-4002 Basel/Switzerland
Submitter's Telephone Number:	++41 61 706 48 48
Submitter's Contact:	Reto Schöni, PhDRegulatory Affairs Specialist Diagnostics,R&D Hemostasis and Test Kit Development
Date of 510(k) Preparation:	September 30, 2004

1. Name of the device, including the trade or proprietary name, the common or usual name and the classification name

Trade or Proprietary Name:	Pefakit® APC-R Factor V Leiden Controls
Common or Usual Name:	Quality Control Plasmas
Classification Name:	Hematology, Factor deficiency test

3. Identification of the legally marketed device to which the submitter claims substantial equivalence

Predicate Device Name:	COATEST® APCTM RESISTANCE V /COATEST® APCTM RESISTANCE VS
510(k) Number:	K963111
Regulation Number:	864.7925
Regulatory Class:	II

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4. Description of the device

Pefakit® APC-R Factor V Leiden Controls is an in vitro diagnostic controls kit containing 3 vials each of the following 2 Ivophilized plasmas:

C1: pooled human plasma from donors confirmed to be normal wild-type by FV Leiden PCR testing

C2: pooled human plasma from donors confirmed to be heterozygous by FV Leiden PCR testing.

5. Statement on the intended use of the device

The device is a kit containing pooled plasmas from donors genotyped for the factor V Leiden mutation (FV:Q506). Controls contain pooled plasmas of either donors with heterozygous FV:Q506 mutation or normal wild-type pattern. These controls are intended to be used in connection with the device Pefakit® APC-R Factor V Leiden.

6. Summary of the technological characteristics of the new device in comparison to those of the predicate device

The predicate device COATEST® APC™ RESISTANCE V / COATEST® APC™ RESISTANCE VS contains plasmas of the FV-L wild-type/normal (level 1) and FV-L heterozygous (level 2) type as controls. They are an integrated part of this test device. For 'Pefakit® APC-R Factor V Leiden' the controls are offered as a separate kit named 'Pefakit® APC-R Factor V Leiden Controls', being object of the present submission. Unlike calibrators which normally represent a quantitative property of the analyte these controls stand for a qualitative property (genotype) of the analyte. Controls for FV-L APC resistance testing in general are used to verify that the clotting time and ratio values obtained for the different FV-L genotypes remain within a predefined range established for the specific laboratory and a specific instrument. They are thus used for quality control and for validation of the basic test reagents before and/or after each test run.

With respect to material, presentation, purpose, safety, preparation and handling the lyophilized plasmas C1 (FV-L Negative Control) and C2 (FV-L Heterozygous Control) controls are substantially equivalent to level 2 control plasmas of the predicate device. The different ranges of expected values are a result of differences in the test principle between the two basic tests.

The material of both devices compared is derived from pooled human plasma genotyped with an approved PCR test specific for the Factor V Leiden mutation. It has been screened for absence of viruses (HIV1&2, HCV, HBV, and HTLV I&II) by FDAapproved methods. Since no screening layout can completely rule out the presence of blood borne diseases, both devices carry the warning information, that the material is derived from human blood and has therefore to be handled as potentially infectious material.

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Part B

1. Brief discussion of the non-clinical tests submitted, referenced , or relied on in the premarket notification submission for a determination of substantial equivalence
  Non-clinical tests were done in-house to determine stability and batch-to-batch variability. The control plasmas have shown to be very stable under different conditions relevant for their use and storage. On-board stability of the reconstituted controls is at least 8h which is equivalent or even superior to what has been claimed for the predicate device. Reconstituted and frozen plasmas are stable at -20℃ for at least 6 months, compared to 3 months for the controls in the predicate device. Real time long-term stability studies for the kit and its control plasmas are still ongoing, but so far the kit proved to be stable for 2 years when stored unopened at 2-8°C.

Batch-to-batch variability has been demonstrated to be very low on three pilot batches of increasing size (100, 250, and 1000 device boxes) of both the basic device and the control device.

2. Brief discussion of the clinical tests submitted, referenced or relied on in the premarket notification submission for a determination of substantial equivalence

The Pefakit® APC-R Factor V Leiden was compared side-by-side with the predicate device COATEST® APC™ RESISTANCE V in clinical studies at two haematology laboratories of big central Hospitals in Europe (Clinical Institute for Medical and Chemical Laboratory Diagnostics/Allgemeines Krankenhaus [CIMCLD/AKH], Vienna) and the USA (Duke University Medical Center [DUMC], Durham/Raleigh NC). The results of these studies have been given and discussed in a separate 510(k) submission for the basic test device. The respective controls have been used in these studies for quality control and reagent validation. The Pefakit® control plasmas proved to be suitable for their intended use and to be equivalent to the control plasmas in the predicate device.

1. Conclusions drawn from the non-clinical and clinical tests that demonstrate that the device is as safe, as effective, and as well or better than the legally marketed device identified in part A (3)
  The control plasmas of 'Pefakit® APC-R Factor V Leiden Controls' and the control plasmas included in the predicate device 'COATEST APC™ RESISTANCE V' are equivalent in terms of intended use, safety of use and overall qualitative characteristics.

N. Peterson

Reto Schöni, Ph. D.

September 30, 2004

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles three intertwined human profiles or a caduceus-like design.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 22 2004

Pentapharm Ltd. c/o Ms. M. Elisabeth Bierman Morgan, Lewis & Bockius LLP. 1111 Pennsylvania Avenue., NW Washington DC 20004

Re: K042760

Trade/Device Name: Pefakit® APC-R Factor V Leiden Controls Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: GGN Dated: December 7, 2004 Received: December 9, 2004

Dear Ms. Bierman:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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Page 2

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Robert L. Becker Jr.

Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): _K042760

Device Name:

Pefakit® APC-R Factor V Leiden Controls

Indications For Use:

The device is a box containing lyophilized pooled plasmas from donors genotyped for the factor V Leiden mutation (FV : Q506) to be reconstituted with water by the user. Controls on the factor
plasmas of either donors with helerazurous EV: O56 minuter by the user. Con plasmas of either donors with heterozygous FV:Q506 mutation or normal wild-type pattern.
These controls are intended to be your for wolf These controls are intended to be used for quality assurance in connection with the IVD device 'Pefakit® APC-R Factor V Leiden'.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF

NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K042760

Page 1 of _________

Regulation Number and Section

§ 864.5425 Multipurpose system for in vitro coagulation studies.

(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.